The causal relationship of basal metabolic rate with susceptibility and 28-day mortality risk of sepsis based on a two-sample bidirectional Mendelian randomization method
Objective To investigate the causal relationship of basal metabolic rate(BMR)with susceptibility and 28-day mortality risk of sepsis.Methods Three groups of large-scale genome-wide association study(GWAS)summary data of BMR,sepsis and 28-day mortality of sepsis were obtained from the publicly available UK Biobank to perform a two-sample bidirectional Mendelian randomization(MR)analysis.Inverse-variance weighting(IVW)was employed as the primary method for MR analysis,supplemented by four methods including MR-Egger regression,weighted median,simple mode and weighted mode.Horizontal pleiotropy was assessed by using the MR-Egger intercept test and MR pleiotropy residual sum and outlier(MR-PRESSO)test,respectively.Additionally,heterogeneity was assessed by using the Cochrane's Q test.Finally,sensitivity analysis was performed by using the leave-one-out method.Results A total of 515 single nucleotide polymorphisms associated with BMR were screened as instrumental variables.For sepsis susceptibility,IVW method revealed a causal relationship between genetically predicted high levels of BMR and increased sepsis susceptibility(OR=1.364,95％CI 1.226-1.518,P＜0.001).For the risk of 28-day mortality,IVW method revealed a causal relationship between genetically predicted high levels of BMR and an increased risk of 28-day mortality(OR=1.324,95％CI 1.023-1.713,P=0.002).Reverse MR analysis showed no causal relationship of susceptibility and 28-day mortality of sepsis with BMR(P＞0.05).The MR-Egger intercept test and the MR-PRESSO test showed there wes no bias in causal estimation in terms of horizontal pleiotropy.Cochrane's Q test demonstrated no heterogeneity between instrumental variables.In addition,sensitivity analysis substantiated the robustness of two MR analysis findings.Conclusions There is a causal relationship of genetically predicted high levels of BMR with increased susceptibility and 28-day mortality risk of sepsis,indicating that BMR management might be beneficial to reducing the morbidity and mortality of sepsis.
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